High-resolution Tandem Mass Spectrometry for Studying Chemical Constituents of Gynura bicolor DC.

The separation and analysis of the desired chemical components are important subjects for the fundamental research of traditional Chinese medicine (TCM). Ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) has gradually become a leading technology for the identification of TCM ingredients. Gynura bicolor DC. (BFH), a perennial stemless herb used for medicine and food in China has medicinal effects such as clearing heat, moistening the lung, relieving cough, dispersing stasis, and relieving swelling. Polyphenols and flavonoids contain numerous isomers, which hinder the identification of the complex compounds in BFH. This paper presents a systematic protocol for studying chemical constituents of BFH based on solvent extraction and integrated data via UPLC-Q-TOF-MS. The method described here includes systematic protocols for sample pretreatment, MS calibration, MS acquisition, data processing, and analysis of results. Sample pretreatment includes collection, cleaning, drying, crushing, and extraction. MS calibration consists of multipoint and single-point correction. Data processing includes data importing, method establishment, analysis processing, and result presentation. Representative results of the typical fragmentation pattern of phenolic acids, esters, and glycosides in Gynura bicolor DC. (BFH) are presented in this paper. In addition, organic solvent selection, extraction, data integration, collision energy selection, and method improvement are discussed in detail. This universal protocol can be widely used to identify complex compounds in TCM.

Miniaturized and highly-sensitive fiber-optic photoacoustic gas sensor based on an integrated tuning fork by mechanical processing with dual-prong differential measurement.

A proof-of-concept gas sensor based on a miniaturized and integrated fiber-optic photoacoustic detection module was introduced and demonstrated for the purpose of developing a custom tuning-fork (TF)-enhanced photoacoustic gas sensor. Instead of piezoelectric quartz tuning fork (QTF) in conventional quartz-enhanced photoacoustic spectroscopy (QEPAS), a low-cost custom aluminum alloy TF fabricated by mechanical processing was employed as a photoacoustic transducer and the vibration of TF was measured by fiber-optic Fabry-Pérot (FP) interferometer (FPI). The mechanical processing-based TF design scheme greatly increases the flexibility of the TF design with respect to the complex and expensive manufacture process of custom QTFs, and thus it can be better exploited to detect gases with slow vibrational-translational (V-T) relaxation rates and combine with light sources with poor beam quality. The resonance frequency and the quality factor of the designed custom TF at atmospheric pressure were experimentally determined to be 7.3 kHz and 4733, respectively. Dual-prong differential measurement method was proposed to double the photoacoustic signal and suppress the external same-direction noise. After detailed optimizing and investigating for the operating parameters by measuring H2O, the feasibility of the developed sensor for gas detection was demonstrated with a H2O minimum detection limit (MDL) of 1.2 ppm, corresponding to a normalized noise equivalent absorption (NNEA) coefficient of 3.8 × 10-8 cm-1 W/Hz1/2, which are better than the QTF-based photoacoustic sensors. The proposed gas sensing approach combined the advantages of QEPAS and fiber-optic sensing, which can greatly expand the application domains of PAS-based gas sensors.

Intercellular competitive growth dynamics with microenvironmental feedback.

Normal life activities between cells rely crucially on the homeostasis of the cellular microenvironment, but aging and cancer will upset this balance. In this paper we introduce the microenvironmental feedback mechanism to the growth dynamics of multicellular organisms, which changes the cellular competitive ability and thereby regulates the growth of multicellular organisms. We show that the presence of microenvironmental feedback can effectively delay aging, but cancer cells may grow uncontrollably due to the emergence of the tumor microenvironment (TME). We study the effect of the fraction of cancer cells relative to that of senescent cells on the feedback rate of the microenvironment on the lifespan of multicellular organisms and find that the average lifespan shortened is close to the data for non-Hodgkin's lymphoma in Canada from 1980 to 2015. We also investigate how the competitive ability of cancer cells affects the lifespan of multicellular organisms and reveal that there is an optimal value of the competitive ability of cancer cells allowing the organism to survive longest. Interestingly, the proposed microenvironmental feedback mechanism can give rise to the phenomenon of Parrondo's paradox: When the competitive ability of cancer cells switches between a too-high and a too-low value, multicellular organisms are able to live longer than in each case individually. Our results may provide helpful clues for targeted therapies aimed at the TME.

All-optical non-resonant photoacoustic spectroscopy for multicomponent gas detection based on aseismic photoacoustic cell.

An all-optical non-resonant photoacoustic spectroscopy system for multicomponent gas detection based on a silicon cantilever optical microphone (SCOM) and an aseismic photoacoustic cell is proposed and demonstrated. The SCOM has a high sensitivity of over 96.25 rad/Pa with sensitivity fluctuation less than ± 1.56 dB between 5 Hz and 250 Hz. Besides, the minimal detectable pressure (MDP) of the sensor is 0.55 µPa·Hz-1/2 at 200 Hz, which indicates that the fabricated sensor has high sensitivity and low noise level. Six different gases of CO2, CO, CH4, C2H6, C2H4, C2H2 are detected at the frequency of 10 Hz, whose detection limits (3σ) are 62.66 ppb, 929.11 ppb, 1494.97 ppb, 212.94 ppb, 1153.36 ppb and 417.61 ppb, respectively. The system achieves high sensitivity and low detection limits for trace gas detection. In addition, the system exhibits seismic performance with suppressing vibration noise by 4.5 times, and achieves long-term stable operation. The proposed non-resonant all-optical PAS multi-component gas detection system exhibits the advantages of anti-vibration performance, low gas consumption and long term stability, which provides a solution for working in complex environments with inherently safe.

Ultra High-Performance Liquid Chromatography-Mass Spectrometry and Self-established Database Analysis of Chinese Herbal Medicine Components.

Chinese herbal medicine is complex and has numerous unknown compounds, making qualitative research crucial. Ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) is the most widely used method in qualitative analysis of compounds. The method includes standardized and programmed protocols for sample pretreatment, MS tune, MS acquisition, and data processing. The sample pretreatments include collection, pulverization, solvent extraction, ultrasound, centrifugation, and filtration. Data post-processing was described in detail and includes data importing, self-established database construction, method establishment, data processing, and other manual operations. The above-ground part of the alpine yarrow herb, Achillea millefolium L., is used to treat inflammation, gastrointestinal disturbances, and pain and its 3-oxa-guaianolides could be useful leads for anti-inflammatory drug development. Three representative compounds in AML were identified, combining TOF-MS with a self-established database. Moreover, the differences from existing literature, liquid-phase parameter optimization, scan mode selection, ion source suitability, collision energy adjustment, isomer screening, method limitation, and possible solutions were discussed. This standardized analysis method is universal and can be applied to identify complex compounds in Chinese herbal medicine.

Mechanical force drives the initial mesenchymal-epithelial interaction during skin organoid development.

Rationale: Stem cells self-organize to form organoids that generate mini-organs that resemble the physiologically-developed ones. The mechanism by which the stem cells acquire the initial potential for generating mini-organs remains elusive. Here we used skin organoids as an example to study how mechanical force drives initial epidermal-dermal interaction which potentiates skin organoids to regenerate hair follicles. Methods: Live imaging analysis, single-cell RNA-sequencing analysis, and immunofluorescence were used to analyze the contractile force of dermal cells in skin organoids. Bulk RNA-sequencing analysis, calcium probe detection, and functional perturbations were used to verify that calcium signaling pathways respond to the contractile force of dermal cells. In vitro mechanical loading experiment was used to prove that the stretching force triggers the epidermal Piezo1 expression which negatively regulates dermal cell attachment. Transplantation assay was used to test the regenerative ability of skin organoids. Results: We found that dermal cell-derived contraction force drives the movement of dermal cells surrounding the epidermal aggregates to trigger initial mesenchymal-epithelial interaction (MEI). In response to dermal cell contraction force, the arrangement of the dermal cytoskeleton was negatively regulated by the calcium signaling pathway which further influences dermal-epidermal attachment. The native contraction force generated from the dermal cell movement exerts a stretching force on the adjacent epidermal cells, activating the stretching force sensor Piezo1 in the epidermal basal cells during organoid culture. Epidermal Piezo1 in turn drives strong MEI to negatively regulate dermal cell attachment. Proper initial MEI by mechanical-chemical coupling during organoid culture is required for hair regeneration upon transplantation of the skin organoids into the back of the nude mice. Conclusion: Our study demonstrated that mechanical-chemical cascade drives the initial event of MEI during skin organoid development, which is fundamental to the organoid, developmental, and regenerative biology fields.

Comprehensive analysis of prognostic value and immunotherapy prospect of brain cytoplasmic RNA1 in hepatocellular carcinoma.

BACKGROUND: The expression of brain cytoplasmic RNA1 (BCYRN1) is linked to the clinicopathology and prognosis of several types of cancers, among which hepatocellular carcinoma (HCC) is one of the most frequent types of cancer worldwide. AIM: To explore the prognostic value and immunotherapeutic potential of BCYRN1 in HCC by bioinformatics and meta-analysis. METHODS: Information was obtained from the Cancer Genome Atlas database. First, the correlation between BCYRN1 expression and prognosis and clinicopathologic characteristics of HCC patients was explored. Univariate and multivariate regression analyses were employed to examine the relationship between BCYRN1 and HCC prognosis. Secondly, potential functions and pathways were explored by means of enrichment analysis of differentially-expressed genes. The relationships between BCYRN1 expression and tumor microenvironment, immune cell infiltration, immune checkpoint, drug sensitivity and immunotherapy effect were also investigated. Finally, three major databases were searched and used to conduct a meta-analysis on the relationship between BCYRN1 expression and patient prognosis. RESULTS: BCYRN1 expression was significantly higher in HCC compared to normal tissues and was linked to a poor prognosis and clinicopathological characteristics. Enrichment analysis showed that BCYRN1 regulates the extracellular matrix and transmission of signaling molecules, participates in the metabolism of nutrients, such as proteins, and participates in tumor-related pathways. BCYRN1 expression was linked to the tumor microenvironment, immune cell infiltration, drug sensitivity and the efficacy of immunotherapy. Furthermore, the meta-analysis in this study showed that BCYRN1 overexpression was related to a worse outcome in HCC patients. CONCLUSION: Overexpression of BCYRN1 relates to poor prognosis and may be a potential prognostic factor and immunotherapeutic target in HCC.

Mechanical stimuli-induced CCL2 restores adult mouse cells to regenerate hair follicles.

Aged cells have declined regenerative ability when subjected to environmental insult. Here we elucidate the mechanism by which mechanical stimulus induces hair regeneration at the microenvironmental regulation level using the hair plucking and organoid culture models. We observed that the skin cells harvested from post-plucking day 3 (PPD3) have the best self-organizing ability during skin organoid culture and have the highest hair regeneration upon transplantation. By bulk RNA sequencing (RNA-seq) and single-cell RNA-seq analysis and in situ hybridization, we identified that the chemokine signaling pathway genes including CCL2 are significantly increased in the skin at PPD3 and in skin organoid cultures. Immunostaining shows that the PPD3 skin epithelial cells have increased multipotency, which is verified by the ability to self-organize to form epidermal aggregates during organoid culture. By adding CCL2 recombinant protein to the organoid culture using an environmental reprogramming protocol, we observed the PPD0 adult skin cells, which lose their regenerative ability can self-organize in organoid culture and regenerate hair follicles robustly upon transplantation. Our study demonstrates that CCL2 functions in immune regulation of hair regeneration under mechanical stimulus, and enhances cell multipotency during organoid culture. This provides a therapeutic potential for future clinical application.

Traditional Chinese Medicine has great potential as candidate drugs for lung cancer: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: With high mortality and morbidity rates, lung cancer (LC) has become one of the major threats to human health. The treatment strategies for LC currently face issues, such as drug resistance and body tolerance. Traditional Chinese medicine (TCM) is characterized by novel pharmacological mechanisms, low toxicity, and limited side effects. TCM includes a substantial number of biologically active ingredients, several of which are effective monomeric agents against LC. An increasing number of researchers are focusing their efforts on the discovery of active anti-cancer ingredients in TCM. AIM OF THE REVIEW: In this review, we summarized the anti-LC mechanisms of five types of TCM monomeric compounds. Our goal is to provide research ideas for the identification of new prospective medication candidates for the treatment of LC. MATERIALS AND METHODS: We collected reports on the anti-LC effects of TCM monomers from web databases, including PubMed, Science Direct, Web of Science, and Europe PubMed Central. Among the keywords used were "lung cancer," "traditional Chinese medicine," "pharmacology," and their combinations thereof. Then, we systematically summarized the anti-LC efficacy and related mechanisms of TCM monomers. RESULTS: Based on the available literature, this paper reviewed the therapeutic effects and mechanisms of five types of TCM monomers on LC. The characteristics of TCM monomers include the capabilities to suppress the tumor cell cycle, inhibit proliferation, induce apoptosis, promote autophagy, inhibit tumor cell invasion and metastasis, and enhance efficacy or reduce drug resistance when combined with cytotoxic agents and other methods to arrest the progression of LC and prolong the survival of patients. CONCLUSIONS: TCM contains numerous flavonoids, alkaloids, terpenoids, polyphenols, and other active compounds that are effective against LC. Given their chemical structure and pharmacological properties, these monomers are suitable as candidate drugs for the treatment of LC.

Ajuforrestin A, an Abietane Diterpenoid from Ajuga ovalifolia var. calanthe, Induces A549 Cell Apoptosis by Targeting SHP2.

The Src-homology 2 domain-containing phosphatase 2 (SHP2), which is encoded by PTPN11, participates in many cellular signaling pathways and is closely related to various tumorigenesis. Inhibition of the abnormal activity of SHP2 by small molecules is an important part of cancer treatment. Here, three abietane diterpenoids, named compounds 1-3, were isolated from Ajuga ovalifolia var. calantha. Spectroscopic analysis was used to identify the exact structure of the compounds. The enzymatic kinetic experiment and the cellular thermal shift assay showed compound 2 selectively inhibited SHP2 activity in vitro. Molecular docking indicated compound 2 targeted the SHP2 catalytic domain. The predicted pharmacokinetic properties by SwissADME revealed that compound 2 passed the majority of the parameters of common drug discovery rules. Compound 2 restrained A549 proliferation (IC50 = 8.68 ± 0.96 µM), invasion and caused A549 cell apoptosis by inhibiting the SHP2-ERK/AKT signaling pathway. Finally, compound 2 (Ajuforrestin A) is a potent and efficacious SHP2 inhibitor and may be a promising compound for human lung epithelial cancer treatment.

All-optical light-induced thermoacoustic spectroscopy for remote and non-contact gas sensing.

All-optical light-induced thermoacoustic spectroscopy (AO-LITS) is reported for the first time for highly sensitive and selective gas sensing, in which a commercial standard quartz tuning fork (QTF) is employed as a photothermal detector. The vibration of the QTF was measured by the highly sensitive fiber-optic Fabry-Pérot (FP) interferometry (FPI) technique, instead of the piezoelectric detection in the conventional LITS. To improve the stability of the sensor system, a compact QTF-based fiber-optic FPI module is fabricated by 3D printing technique and a dual-wavelength demodulation method with the ellipse-fitting differential-cross-multiplication algorithm (DW-EF-DCM) is exploited for the FPI measurement. The all-optical detection scheme has the advantages of remote detection and immunity to electromagnetic interference. A minimum detection limit (MDL) of 422 ppb was achieved for hydrogen sulfide (H2S), which was ~ 3 times lower than a conventional electrical LITS sensor system. The AO-LITS can provide a promising approach for remote and non-contact gas sensing in the whole infrared spectral region.

Small-volume highly-sensitive all-optical gas sensor using non-resonant photoacoustic spectroscopy with dual silicon cantilever optical microphones.

A small-volume highly-sensitive photoacoustic spectroscopy (PAS) methane detection system based on differential silicon cantilever optical microphones (SCOMs) is proposed and experimentally demonstrated. The system contains a compact non-resonant photoacoustic cell with a small volume of 1.2 mL and symmetrically-located dual SCOMs, as well as a distributed feedback laser at 1650.96 nm. The two identical SCOMs utilize the Fabry-Perot interferometric fiber-optic structure, with the differential Q-point demodulation algorithm to suppress the external vibration noise. Experimental results show that the SCOM has a high displacement sensitivity about 7.1 µm/Pa at 150 Hz and within 2.5 dB fluctuation between 5 Hz and 250 Hz. In the PAS gas sensing experiment, the normalized noise equivalent absorption coefficient of the PAS system is estimated to be 1.2 × 10-9 cm-1·W·Hz-1/2 and the minimum detection limit for methane is about 111.2 ppb with 1 s integration time. External disturbance is also applied to the dual SCOM system and results show excellent stability and noise resistance. The proposed PAS system exhibits superiorities of low gas consumption, high sensitivity and immunity to vibration and electromagnetic interference, which has an enormous potential in medicine, industry and environment.

Calcium Overload or Underload? The Effects of Doxorubicin on the Calcium Dynamics in Guinea Pig Hearts.

The severe doxorubicin (DOXO) side effect of cardiomyopathy limits it clinical application as an effective anticancer drug. Although Ca2+ overload was postulated as one of the mechanisms for this toxicity, its role was, however, disputable in terms of the contractile dysfunction. In this work, the dynamics of the intracellular Ca2+ signal were optically mapped in a Langendorff guinea pig heart. We found that DOXO treatment: (1) Delayed the activation of the Ca2+ signal. With the reference time set at the peak of the action potential (AP), the time lag between the peak of the Ca2+ signal and AP (Ca-AP-Lag) was significantly prolonged. (2) Slowed down the intracellular Ca2+ releasing and sequestering process. Both the maximum rising (MRV) and falling (MFV) velocity of the Ca2+ signal were decreased. (3) Shortened the duration of the Ca2+ signal in one cycle of Ca2+ oscillation. The duration of the Ca2+ signal at 50% amplitude (CaD50) was significantly shortened. These results suggested a reduced level of intracellular Ca2+ after DOXO treatment. Furthermore, we found that the effect of tachypacing was similar to that of DOXO, and, interestingly, DOXO exerted contradictory effects on the tachypaced hearts: it shortened the Ca-AP-Lag, accelerated the MRV and MFV, and prolonged the CaD50. We, therefore, concluded that DOXO had a different effect on intracellular Ca2+. It caused Ca2+ underload in hearts with sinus rhythm; this might relate to the contractile dysfunction in DOXO cardiomyopathy. It led to Ca2+ overload in the tachypaced hearts, which might contribute to the Ca2+-overload-related toxicity.

Comparison between laparoscopic uncut Roux-en-Y and Billroth II with Braun anastomosis after distal gastrectomy: A meta-analysis.

BACKGROUND: Conventional Billroth II (BII) anastomosis after laparoscopic distal gastrectomy (LDG) for gastric cancer (GC) is associated with bile reflux gastritis, and Roux-en-Y anastomosis is associated with Roux-Y stasis syndrome (RSS). The uncut Roux-en-Y (URY) gastrojejunostomy reduces these complications by blocking the entry of bile and pancreatic juice into the residual stomach and preserving the impulse originating from the duodenum, while BII with Braun (BB) anastomosis reduces the postoperative biliary reflux without RSS. Therefore, the purpose of this study was to compare the efficacy and safety of laparoscopic URY with BB anastomosis in patients with GC who underwent radical distal gastrectomy. AIM: To evaluate the value of URY in patients with GC. METHODS: PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, Chinese Biomedical Database, and VIP Database for Chinese Technical Periodicals (VIP) were used to search relevant studies published from January 1994 to August 18, 2021. The following databases were also used in our search: Clinicaltrials.gov, Data Archiving and Networked Services, the World Health Organization International Clinical Trials Registry Platform Search Portal (https://www.who.int/clinical-trials-registry-platform/the-ictrp-search-portal), the reference lists of articles and relevant conference proceedings in August 2021. In addition, we conducted a relevant search by Reference Citation Analysis (RCA) (https://www.referencecitationanalysis.com). We cited high-quality references using its results analysis functionality. The methodological quality of the eligible randomized clinical trials (RCTs) was evaluated using the Cochrane Risk of Bias Tool, and the non-RCTs were evaluated using the Newcastle-Ottawa scale. Statistical analyses were performed using Review Manager (Version 5.4). RESULTS: Eight studies involving 704 patients were included in this meta-analysis. The incidence of reflux gastritis [odds ratio = 0.07, 95% confidence interval (CI): 0.03-0.19, P < 0.00001] was significantly lower in the URY group than in the BB group. The pH of the postoperative gastric fluid was lower in the URY group than in the BB group at 1 d [mean difference (MD) = -2.03, 95%CI: (-2.73)-(-1.32), P < 0.00001] and 3 d [MD = -2.03, 95%CI: (-2.57)-(-2.03), P < 0.00001] after the operation. However, no significant difference in all the intraoperative outcomes was found between the two groups. CONCLUSION: This work suggests that URY is superior to BB in gastrointestinal reconstruction after LDG when considering postoperative outcomes.

Tumor Microenvironment Stimuli-Responsive Single-NIR-Laser Activated Synergistic Phototherapy for Hypoxic Cancer by Perylene Functionalized Dual-Targeted Upconversion Nanoparticles.

Although synergistic therapy has shown great promise for effective treatment of cancer, the unsatisfactory therapeutic efficacy of photothermal therapy/photodynamic therapy is resulted from the absorption wavelength mismatch, tumor hypoxia, photosensitizer leakage, and inability in intelligent on-demand activation. Herein, based on the characteristics of tumor microenvironment (TME), such as the slight acidity, hypoxia, and overexpression of H2 O2 , a TME stimuli-responsive and dual-targeted composite nanoplatform (UCTTD-PC4) is strategically explored by coating a tannic acid (TA)/Fe3+ nanofilm with good biocompatibility onto the upconversion nanoparticles in an ultrafast, green and simple way. The pH-responsive feature of UCTTD-PC4 remains stable during the blood circulation, while rapidly releases Fe3+ in the slightly acidic tumor cells, which results in catalyzing H2 O2 to produce O2 and overcoming the tumor hypoxia. Notably, the emission spectrum of the UCTTD perfectly matches the absorption spectrum of the photosensitizer (perylene probe (PC4)) to achieve the enhanced therapeutic effect triggered by a single laser. This study provides a new strategy for the rational design and development of the safe and efficient single near-infrared laser-triggered synergistic treatment platform for hypoxic cancer under the guidance of multimodal imaging.

GM-CSF-miRNA-Jak2/Stat3 Signaling Mediates Chemotherapy-Induced Cancer Cell Stemness in Gastric Cancer.

Chemotherapy serves as the first choice in clinic to treat advanced gastric cancer. However, emerging evidence indicated the induction of drug resistance and cancer stem cells occasionally by chemotherapy, which seriously limit the therapeutic effects, but the regulatory mechanism remains unclear. Here we treated two human gastric cancer cell lines SGC7901 and BGC823 with 5-Fluorouracil (5-Fu) or Cisplatin (DDP) in vitro. The survived cells showed significant increase of drug resistance, cell stemness and cytokine GM-CSF expression and secretion. As such, GM-CSF was applied to stimulate gastric cancer cells, followed by the subpopulation of CD133 + CSC analysis, sphere formation assay and stemness genes expression analysis. As a result, CSCs showed induction by GM-CSF treatment. A gastric cancer animal model further indicated that the gastric cancer cells significantly promoted tumor growth after GM-CSF treatment in vivo. High-throughput miRNA and mRNA sequencing analyses identified a subset of miRNAs and mRNAs under regulation of both 5-Fu and GM-CSF in gastric cancer cells, including upregulation of miR-877-3p and downregulation of SOCS2. Targeted overexpression or knockdown of miR-877-3p in gastric cancer cells revealed the oncogenic function of miR-877-3p in regulating gastric cancer by suppressing target gene SOCS2. Jak2/Stat3 signaling pathway, as a downstream target of SOCS2, showed activation in vitro and in vivo after treatment with miR-877-3p or GM-CSF. Our findings not only revealed a novel mechanism through which chemotherapy induced CSCs in gastric cancer via GM-CSF-miRNA-Jak2/Stat3 signaling, but also provided an experimental evidence for appropriate dose reduction of adjuvant chemotherapy in treatment of cancer patients.

Identification of IMPA2 as the hub gene associated with colorectal cancer and liver metastasis by integrated bioinformatics analysis.

BACKGROUND AND OBJECTIVES: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide with high incidence and mortality rate, while colorectal liver metastasis (CRLM) is one of the major causes of cancer-related deaths. Therefore, the present study aims to identify the hub gene associated with CRC carcinogenesis and liver metastasis, and then explore its diagnostic and prognostic value as well as the potential regulation mechanism. METHODS: The overlapping differential co-expression genes among CRC, CRLM, and normal tissues were explored on the GSE49355 and GSE81582 datasets from the Gene Expression Omnibus (GEO) database by integrated bioinformatics analysis. Then, the hub prognostic genes were selected from the overlapping genes by univariate Cox proportional hazard analysis and online database Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Subsequently, the clinical value of the hub genes was evaluated in the TCGA and GSE39582 cohorts. Finally, the underlying mechanisms of the hub gene regulating CRC carcinogenesis and metastasis were explored by Gene function annotation and DNA methylation analysis. RESULTS: Inositol mono-phosphatase 2 (IMPA2) was identified as the hub gene associated with CRC carcinogenesis and liver metastasis. IMPA2 had an excellent diagnostic efficiency, and its expression was significantly decreased in CRC and liver metastasis samples, being positively correlated with poor prognosis. Moreover, its low expression was associated with AJCC stage III+IV, T4, N1+2, and M1. In addition, our results revealed that the potential mechanisms used by IMPA2 to mediate CRC carcinogenesis and metastasis could be associated with lipid metabolism and epithelial mesenchymal transition (EMT). Finally, IMPA2 expression could be regulated by DNA methylation. CONCLUSIONS: IMPA2 was identified and reported for the first time as a hub gene biomarker in the diagnosis and prognosis of CRC, which could regulate CRC carcinogenesis and liver metastasis through the regulation of lipid metabolism, EMT, and DNA methylation.

DSP-free remote antenna unit in a coherent radio over fiber mobile fronthaul for 5G mm-wave mobile communication.

We propose a novel coherent analog radio over fiber (A-RoF) scheme to realize the generation, separation, and detection of four-independent mm-wave signals with the same carrier frequency on a single-wavelength for 5th generation (5G) mobile communication, and no digital signal processing (DSP) algorithms are required in remote antenna unit (RAU). In baseband unit (BBU), four-independent mm-wave signals are modulated on the two orthogonal polarization states of a single wavelength based on a dual-polarization IQ modulator using the dual single-sideband (SSB) modulation and polarization division multiplexing (PDM) technique. In RAU, a novel carrier polarization rotation module based on the self-polarization stabilization technique is proposed, and thus the four-independent mm-wave signals can be detected by self-coherent detection. Besides, the power fading effect induced by the chromatic dispersion could be overcome thanks to the optical SSB modulation, contributing to the increased coverage. By these means, no DSP algorithms are required in RAU, and the latency of signal processing could be significantly reduced. The experimental results show our proposed scheme could support 38.4 Gbps 16-ary quadrature amplitude modulation (16QAM) signals at 14 GHz over 30 km standard single-mode fiber (SSMF) transmission without DSP, satisfying 3rd Generation Partnership Project (3GPP) requirements. Besides, the measured error vector magnitude (EVM) value of 800 MBaud 16QAM signals at 28 GHz over 50 km SSMF transmission is 12.99%. This research provides a potential solution for the 5G mobile fronthaul.

Oleanolic acid inhibits the migration and invasion of hepatocellular carcinoma cells by promoting microRNA-122 expression.

MicroRNAs are emerging as important endogenous regulators of gene function and they are playing an important role in the occurrence and development of cancer. They are also regarded as robust biomarkers of cancer diagnosis and prognosis. Hepatocellular carcinoma (HCC) is a common and complex human malignancy with high mortality and morbidity in the world. MicroRNA-122 (miR-122) is a liver-specific microRNA and is closely associated with HCC metastasis, which makes miR-122 a promising target for drug design and development. In this study, we performed a cell-based screening method for discovering miR-122 activators and found that oleanolic acid (OA), a natural pentacyclic triterpene, specifically increased miR-122 expression in a concentration-dependent manner. Two HCC cell lines (HepG2 and Sk-hep-1 cells) were used to evaluate the effect of OA on cell migration and invasion abilities. The results indicated that OA attenuated the migration and invasion abilities of HCC cells by upregulating miR-122 expression. In addition, OA increased the expression of E-cadherin and decreased the expression of ß-catenin, N-cadherin and vimentin. After knocking down miR-122 with miR-122 inhibitor, we found that the effect of OA on these epithelial-to-mesenchymal transition (EMT) related molecules was significantly weakened, indicating OA exhibited anti-EMT effect by increasing the expression of miR-122. These finding may help to better understand the molecular mechanism of OA's anti-metastasis activity.

Dietary daidzein inhibits hepatitis C virus replication by decreasing microRNA-122 levels.

MicroRNAs are emerging as critical endogenous regulators of gene function. Aberrant regulation of microRNAs is associated with various human diseases, most importantly cancer. MicroRNA-122 (miR-122), a liver-specific microRNA, has been implicated in the control of hepatitis C virus (HCV) RNA replication and its response to interferon (IFN) in human hepatoma cells. Here, we report that daidzein, a naturally occurring plant isoflavone, inhibits HCV replication and enhances the antiviral effect of IFN-α on HCV therapy by decreasing microRNA-122 levels in vitro without significantly affecting cell growth. Moreover, daidzein was found to inhibit the expression of miR-122 and miR-21 by down-regulating the expression of TRBP, indicating that daidzein is possibly a general inhibitor of the miRNA pathway. Thus, daidzein provides new insights for drug discovery and HCV prevention.